Yan'an Hospital Affiliated To Kunming Medical University

The association between abdominal obesity (as measured by waist circumference (WC) and waist-to-hip ratio (WHR)) and colorectal cancer (CRC) has not been fully quantified, and the magnitude of CRC risk associated with abdominal obesity is still unclear. A meta-analysis of prospective studies was performed to elucidate the CRC risk associated with abdominal obesity. Pubmed and Embase were searched for studies assessing the association between abdominal obesity and CRC risk. Relative risks (RRs) with 95% confidence intervals (95% CIs) were pooled using random-effects model of meta-analysis. Nineteen prospective cohort studies from eighteen publications were included in this meta-analysis. A total of 12,837 CRC cases were identified among 1,343,560 participants. Greater WC and WHR were significantly associated with increased risk of total colorectal cancer (WC: RR 1.42, 95% CI 1.30, 1.55; WHR: RR 1.39, 95% CI 1.25, 1.53), colon cancer (WC: RR 1.53, 95% CI 1.36, 1.72; WHR: 1.39, 95% CI 1.18, 1.63), and rectal cancer (WC: RR 1.20, 95% CI 1.03, 1.39; WHR: RR 1.22, 95% CI 1.05, 1.42). Subgroup analyses further identified the robustness of the association above. No obvious risk of publication bias was observed. In summary, abdominal obesity may play an important role in the development of CRC.

Background and Aims Hepatocellular carcinoma (HCC) is associated with high malignancy rates. Recently, a known deacetylase silent information regulator 1 (SIRT1) was discovered in HCC, and its presence is positively correlated with malignancy and metastasis. N 6 ‐methyladenosine (m 6 A) is the most prominent modification, but the exact mechanisms on how SIRT1 regulates m 6 A modification to induce hepatocarcinogenesis remain unclear. Approach and Results Here we demonstrate that SIRT1 exerts an oncogenic role by down‐regulating fat mass and obesity‐associated protein (FTO), which is an m 6 A demethylase. A crucial component of small ubiquitin‐related modifiers (SUMOs) E3 ligase, RANBP2, is activated by SIRT1, and it is indispensable for FTO SUMOylation at Lysine (K)‐216 site that promotes FTO degradation. Moreover, Guanine nucleotide‐binding protein G (o) subunit alpha (GNAO1) is identified as m 6 A downstream targets of FTO and tumor suppressor in HCC, and depletion of FTO by SIRT1 improves m 6 A + GNAO1 and down‐regulates its mRNA expression. Conclusions We demonstrate an important mechanism whereby SIRT1 destabilizes FTO, steering the m 6 A + of downstream molecules and subsequent mRNA expression in HCC tumorigenesis. Our findings uncover a target of SIRT1 for therapeutic agents to treat HCC.

Hypoxia plays a critical role in cancer biology. It induces genomic instability, which in turn helps cancer cells respond adaptively to meet the needs of carcinogenesis, cancer progression and relapse. Circular RNA has not been reported among the variety of downstream factors in this adaptive response. Although a few studies have demonstrated the important role of circular RNAs in driving human bladder cancer progression, their carcinogenic roles are still under investigated. Here, we identified a hypoxia-elevated circular RNA, circELP3, that contributes to bladder cancer progression and cisplatin resistance. Decreasing the level of circELP3 via siRNA clearly reduced the in vitro proliferation and cisplatin resistance of bladder cancer cells and promoted apoptosis. Interfering with circELP3 suppressed tumor xenograft growth in nude mice in vivo. In addition, lower circELP3-expressing bladder cancer cells displayed poorer self-renewal capacity, as demonstrated by lower levels of sphere formation and stem cell marker expression. Furthermore, in human bladder cancer patients, strong correlations between a high circELP3 level and advanced tumor grade and lymph node metastasis were observed. In summary, we provide the first direct evidence that circular RNA participates in the adaptive response to hypoxia and may play a role in the progression and drug resistance of bladder cancer.

Significance Triple-negative breast cancer (TNBC) is responsible for significant mortality among breast cancer subtypes, with its treatment largely unsuccessful due to ineffective targeted therapies. Our bioinformatics analysis demonstrates a unique alternative splicing pattern in TNBC compared with those of other breast cancers. In analyzing the underlying mechanism of the distinct alternative splicing profile, TDP43 , a critical gene previously implicated in neurodegenerative disease, is found to promote TNBC progression. Mechanistically, TDP43 regulates extensive alternative splicing events, including downstream gene PAR3 , by forming a complex with SRSF3 to regulate alternative splicing events coordinately. Splicing factors TDP43 and SRSF3, which are likely responsible for the unique alternative splicing, could serve as potential targets for TNBC therapy.

Carbon dots (CDs) have broad prospective applications in various fields, and expanding the applications of fluorescent CDs, especially for CDs derived from bacteria, is a major research goal. In this study, novel CDs derived from Escherichia coli BW25113 (WT) were successfully synthesized via a one-step hydrothermal method. Unlike previously developed CDs-E. coli, CDs-WT can be used for microbial imaging of both live and dead cells. We demonstrated the biocompatibility, excellent penetrability, and nontoxic characteristics of CDs-WT for use as fluorescent probes for bioimaging both in vitro and in vivo. Importantly, we provide the first demonstration of CDs-WT distribution in various organs of mice, including the ability to cross the blood-brain barrier and the potential for rapid excretion through the intestines. Additionally, CDs-WT can be instantly utilized as a fluorescent probe for the highly selective and rapid detection of p-nitrophenol (p-NP) by the inner filter effect, with a limit of detection for p-NP of 11 nM, the lowest value reported to date. Hence, our results demonstrate the feasibility of p-NP detection and extend the bio-imaging applications of CDs prepared from bacteria.

BACKGROUND: Reactive oxygen species (ROS) levels largely determine pulmonary fibrosis. Antioxidants have been found to ameliorate lung fibrosis after long-term paraquat (PQ) exposure. The effects of antioxidants, however, on the signalling pathways involved in PQ-induced lung fibrosis have not yet been investigated sufficiently. Here, we examined the impacts of ligustrazin on lung fibrosis, in particular ROS-related autophagy and pro-fibrotic signalling pathways, using a murine model of PQ-induced lung fibrosis. METHODS: We explored the effects of microRNA-193 (miR-193a) on Hedgehog (Hh) and PI3K/Akt/mTOR signalling and oxidative stress in lung tissues. Levels of miR-193a, protein kinase B (Akt), phosphoinositide 3-Kinase (PI3K), ceclin1, mammalian target of rapamycin (mTOR), sonic hedgehog (SHH), myosin-like Bcl2 interacting protein (LC3), smoothened (Smo), and glioma-associated oncogene-1 (Gli-1) mRNAs were determined with quantitative real-time PCR. Protein levels of PI3K, p-mTOR, p-Akt, SHH, beclin1, gGli-1, LC3, smo, transforming growth factor-β1 (TGF-β1), mothers against DPP homologue-2 (Smad2), connective tissue growth factor (CTGF), collagen I, collagen III, α-smooth muscle actin (α-SMA) nuclear factor erythroid 2p45-related factor-2 (Nrf2), and p-Smad2 were detected by western blotting. In addition, α-SMA, malondialdehyde, ROS, superoxide dismutase (SOD), oxidised and reduced glutathione, hydroxyproline, and overall collagen levels were identified in lung tissues using immunohistochemistry. RESULTS: Long-term PQ exposure blocked miR-193a expression, reduced PI3K/Akt/mTOR signalling, increased oxidative stress, inhibited autophagy, increased Hh signalling, and facilitated the formation of pulmonary fibrosis. Ligustrazin blocked PI3K/Akt/mTOR and Hh signalling as well as reduced oxidative stress via increasing miR-193a expression and autophagy, all of which reduced pulmonary fibrosis. These effects of ligustrazin were accompanied by reduced TGF-β1, CTGF, and Collagen I and III expression. CONCLUSIONS: Ligustrazin blocked PQ-induced PI3K/Akt/mTOR and Hh signalling by increasing miR-193a expression, thereby attenuating PQ-induced lung fibrosis.

Coagulation balance is maintained through fine-tuned interactions among clotting factors, whose physiological concentrations vary substantially. In particular, the concentrations of coagulation proteases (pM to nM) are much lower than their natural inactivator antithrombin (AT, ~ 3 μM), suggesting the existence of other coordinators. In the current study, we found that transferrin (normal plasma concentration ~40 μM) interacts with fibrinogen, thrombin, factor XIIa (FXIIa), and AT with different affinity to maintain coagulation balance. Normally, transferrin is sequestered by binding with fibrinogen (normal plasma concentration ~10 μM) at a molar ratio of 4:1. In atherosclerosis, abnormally up-regulated transferrin interacts with and potentiates thrombin/FXIIa and blocks AT's inactivation effect on coagulation proteases by binding to AT, thus inducing hypercoagulability. In the mouse model, transferrin overexpression aggravated atherosclerosis, whereas transferrin inhibition via shRNA knockdown or treatment with anti-transferrin antibody or designed peptides interfering with transferrin-thrombin/FXIIa interactions alleviated atherosclerosis. Collectively, these findings identify that transferrin is an important clotting regulator and an adjuster in the maintenance of coagulation balance and modifies the coagulation cascade.

BACKGROUND: Exposure to paraquat results in acute lung injury. A systemic inflammatory response has been widely established as a contributor to paraquat-induced acute lung injury. Recent studies have reported that consumption of Xuebijing prevents inflammatory response-induced diseases. This study investigated whether consumption of Xuebijing protected rats against paraquat-induced acute lung injury. METHODS: Adult male Sprague Dawley rats were randomly divided into four groups: control group; paraquat group; paraquat + Xuebijing group; and paraquat + dexamethasone group. Rats in the paraquat, paraquat + Xuebijing and paraquat + dexamethasone groups were intraperitoneally injected with paraquat (30 mg/kg) or administered paraquat and Xuebijing at 8 mL/kg or dexamethasone at 5 mg/kg, respectively, via an injection into the tail vein. Lung p38 MAPK, NF-κB65, IkB, p-IκB-α, HIF-1α, Nrf2 and TGF-β1 expression were essayed using western blotting. IL-6, TNF-α, IL-1β, IL-10, TGF-β1 and PIIIP were measured using ELISA. ROS, oxidised glutathione and glutathione activity were measured. RESULTS: After inducing acute lung injury with paraquat for 24 h, Xuebijing was observed to block lung p-p38 MAPK, NF-κB65, HIF-1α, p-IκB-α and TGF-β1 expression, and increased Nrf2 and IkB expression. The numbers of neutrophils and lymphocytes and total number of cells were significantly lower in the Xuebijing group compared with the control group. IL-6, TNF-α, IL-1β, TGF-β1 and PIIIP levels were significantly decreased in the Xuebijing group. ROS and oxidised glutathione activity were markedly inhibited by Xuebijing. Histological evaluation showed attenuation of the effects of Xuebijing on paraquat-induced lung injury. Compared with the paraquat + dexamethasone group, the Xuebijing + paraquat group showed no significant differences. CONCLUSIONS: Inhibiting the expression of p38 MAPK and NF-κB65 was crucial for the protective effects of Xuebijing on paraquat-induced acute lung injury. The findings suggest that Xuebijing could effectively ameliorate paraquat-induced acute lung injury in rats. Xuebijing was as effective as dexamethasone at improving paraquat-induced lung injury by regulating lung inflammation, lung function and oxidative stress responses.

Vaccine hesitancy, defined as the reluctance or rejection in receiving a vaccine despite its availability, represents a major challenge to global health efforts aiming to control the ongoing COVID-19 pandemic. Understanding the possible factors correlated with COVID-19 vaccine hesitancy using a refined well-informed approach can be helpful to address the phenomenon. The current study aimed to evaluate COVID-19 vaccine acceptance rates using four hypothetical scenarios of varying levels of vaccine efficacy and safety profiles in ten Asian, African and South American countries. These scenarios included: 95% efficacy and 20% side effects (Vaccine A), 75% efficacy and 5% side effects (Vaccine B); 75% efficacy and 20% side effects (Vaccine C) and 50% efficacy and 5% side effects (Vaccine D). This study used a self-administered online survey that was distributed during February-May 2021. The total number of study respondents was 1337 with countries of residence as follows: India (21.1%), Pakistan (12.9%), Sudan (11.2%), Nigeria (9.3%), Iran (8.2%), Bangladesh and Brazil (7.9%), Chile (7.7%), Tunisia (7.6%), and Egypt (6.2%). The overall acceptance rates for COVID-19 vaccination were variable based on varying degrees of safety and efficacy as follows: 55.6% for Vaccine C, 58.3% for Vaccine D, 74.0% for Vaccine A and 80.1% for Vaccine B. The highest levels of COVID-19 vaccine acceptance were observed in Brazil followed by Chile across the four different safety and efficacy scenarios. The lowest COVID-19 vaccine acceptance rates were reported in Egypt and Tunisia for the low safety scenarios (20% side effects), and the low efficacy scenario (50% efficacy). The study revealed the potential effect of vaccine safety and efficacy on the intention to get COVID-19 vaccination. At the same efficacy level, higher possibility of side effects caused a large drop in COVID-19 vaccine acceptance rate. This indicates the importance of accurate communication regarding vaccine safety and efficacy on attitude towards the vaccine and intentions to get vaccinated. Regional differences in COVID-19 vaccine acceptance were observed with the Middle East/North African countries showing the lowest rates and the South American countries displaying the highest vaccine acceptance rates.

In this study, we aimed at investigating effects of lncRNA ADAMTS9-AS2 on lung cancer progression through regulating miR-223-3p and TGFBR3 expressions. Expressions of ADAMTS9-AS2 in lung cancer tissues and cell lines were determined by reverse transcriptase polymerase chain reaction (qRT-PCR). TargetScan and miRcode were used to predict the targeting relationships, respectively. The luciferase reporter system was used to verify that the relationship among ADAMTS9-AS2, TGFBR3 and miR-223-3p. Western blot assay tested the protein level changes in TGFBR3. Cell proliferation was determined by CCK-8 assay. Cell cycle and cell apoptosis were detected by flow cytometry assay, and migration and invasion were determined by transwell assay. Tumor xenograft model was developed to study the influence of ADAMTS9-AS2 on tumor growth in vivo. qRT-PCR results demonstrated that lncADAMTS9-AS2 was lowly expressed in lung cancer tissues. High expression of ADAMTS9-AS2 in lung cancer cells significantly reduced proliferation ability and inhibited migration, as well as elevating their apoptosis rate. In vivo assay found that ADAMTS9-AS2 suppressed the lung tumor growth. Bioinformatics predicted that miR-223-3p bound directly to the ADAMTS9-AS2 and TGFBR3, which was later confirmed by luciferase reporter system. ADAMTS9-AS2 transfection increased TGFBR3 mRNA and protein expressions in lung cancer cells, but miR-223-3p transfection significantly decreased them. Besides, our results showed that miR-223-3p induced cellular apoptosis while TGFBR3 group showed the complete opposite effect. It was proved that ADAMTS9-AS2 and TGFBR3 were the direct genes of miR-223-3p. MiR-223-3p promotes proliferation, migration and invasion of lung cancer cells by targeting TGFBR3. Therefore, ADAMTS9-AS2, miR-223-3p and TGFBR3 may provide potential targets for the treatment of lung cancer patients. © 2018 IUBMB Life, 70(6):536-546, 2018.

BACKGROUND: Mothers are the primary source of bacteria for newborns, but it is unclear whether mother-to-newborn transmission occurs prior to, during or after birth. Similarly, the effect of the delivery mode on neonatal microorganisms has been the focus of controversy. METHODS: Healthy maternal and neonatal pairs that underwent vaginal birth and caesarean section were enrolled in this study. Meconium, placenta, membrane and amniotic fluid samples for newborns and vaginal, rectal and oral samples for mothers were collected. All samples were amplified and sequenced by a 16S rRNA gene primer set targeting bacteria and archaea. FINDINGS: A total of 550 samples from 36 mother-neonate pairs with vaginal births and 42 mother-neonate pairs with caesarean sections were included in this study. The negative controls showed that the data analysis in this study was not affected by contamination. There was a high diversity of microbial communities in the pregnancy environment of the foetus. Meconium samples could be divided into three distinct types that were not influenced by the delivery method. INTERPRETATION: The distribution patterns of bacterial communities in the meconium, placenta, and foetal membranes were highly similar and had nothing to do with the mode of delivery. For approximately half of the placental microorganisms, the same sequence could be found in the vaginal, rectal, and oral samples of the mother.

// Jin-Fang Jiang 1 , Yong-Cong Lao 1 , Bao-Hong Yuan 2 , Jun Yin 3 , Xin Liu 1 , Long Chen 4 and Jian-Hong Zhong 5 1 Department of Chemotherapy, Affiliated Tumor Hospital of Guangxi Medical University, Nanning, China 2 Department of General Surgery, Yan’An Hospital Affiliated to Kunming Medical University, Kunming, China 3 Department of Radiation Oncology, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China 4 Department of Radiology, Affiliated Tumor Hospital of Guangxi Medical University, Nanning, China 5 Department of Hepatobiliary Surgery, Affiliated Tumor Hospital of Guangxi Medical University, Nanning, China Correspondence to: Jian-Hong Zhong, email: // Long Chen, email: // Keywords : hepatic resection; hepatocellular carcinoma; portal vein tumor thrombosis; transarterial chemoembolization Received : December 28, 2016 Accepted : February 02, 2017 Published : February 16, 2017 Abstract Portal vein tumor thrombus is a frequent, challenging complication in hepatocellular carcinoma. Hepatocellular carcinoma patients with portal vein tumor thrombus may show worse liver function, less treatment tolerance and worse prognosis than patients without portal vein tumor thrombus, and they may be at higher risk of comorbidity related to portal hypertension. Western and some Asian guidelines stratify hepatocellular carcinoma with portal vein tumor thrombus together with metastatic hepatocellular carcinoma and therefore recommend only palliative treatment with sorafenib or other systemic agents. In recent years, more treatment options have become available for hepatocellular carcinoma patients with portal vein tumor thrombus, and an evidence-based approach to optimizing disease management and treatment has become more widespread. Nevertheless, consensus policies for managing hepatocellular carcinoma with portal vein tumor thrombus have not been established. This comprehensive literature review, drawing primarily on studies published after 2010, examines currently available management options for patients with hepatocellular carcinoma and portal vein tumor thrombus.

Human papillomavirus (HPV) infection plays a key role in the development of cervical cancer. The aim of the current study was to investigate the HPV type distribution in Chinese women from Yunnan Province, southwest China. A total of 28,457 individuals ranging in age from 17-84 years were recruited from 13 clinical hospitals located in 10 different regions of Yunnan Province. Cervicovaginal swabs were collected from each participant, and HPV screening was performed using Luminex xMAP technology. Our results showed that the HPV prevalence was 12.9% in Yunnan Province. Overall, 10.6% of the individuals were positive for a single HPV type, and 2.3% were positive for multiple types. Among the individuals who tested positive for a single HPV type and multiple HPV types, the three most prevalent high-risk types were 52, 16, and 58. Age subgroup analysis showed two peaks for the frequencies of single and multiple HPV infections, one for the group of women under 25 years old, and the other for the group over 56 years old. Here, we present data regarding the prevalence and type distribution of HPV infection, which will aid in the estimation of the potential clinical benefit and cost-effectiveness of HPV screening and vaccination in China.

Studies have shown significantly increased thromboembolic events at high altitude. We recently reported that transferrin could potentiate blood coagulation, but the underlying mechanism for high altitude-related thromboembolism is still poorly understood. Here, we examined the activity and concentration of plasma coagulation factors and transferrin in plasma collected from long-term human residents and short-stay mice exposed to varying altitudes. We found that the activities of thrombin and factor XIIa (FXIIa) along with the concentrations of transferrin were significantly increased in the plasma of humans and mice at high altitudes. Furthermore, both hypoxia (6% O2) and low temperature (0°C), 2 critical high-altitude factors, enhanced hypoxia-inducible factor 1α (HIF-1α) levels to promote the expression of the transferrin gene, whose enhancer region contains HIF-1α binding site, and consequently, to induce hypercoagulability by potentiating thrombin and FXIIa. Importantly, thromboembolic disorders and pathological insults in mouse models induced by both hypoxia and low temperature were ameliorated by transferrin interferences, including transferrin antibody treatment, transferrin downregulation, and the administration of our designed peptides that inhibit the potentiation of transferrin on thrombin and FXIIa. Thus, low temperature and hypoxia upregulated transferrin expression-promoted hypercoagulability. Our data suggest that targeting the transferrin-coagulation pathway is a novel and potentially powerful strategy against thromboembolic events caused by harmful environmental factors under high-altitude conditions.

BACKGROUND/AIMS: Autophagy is an evolutionarily conserved catabolic mechanism to maintain energy homeostasis and to remove damaged cellular components, which plays an important role in the survival of various cells. Inhibiting autophagy is often applied as a new strategy to halt the growth of cancer cells. METHODS: The effect of FOXO1 gene on cellular function and apoptosis and its underlying mechanisms were investigated in cultured QBC939 cells by the methylthiazoletetrazolium (MTT) assay, western blot, DCFDA mitochondrial membrane potential, and ATP content measurement. FOXO1 siRNA was applied to down-regulate FOXO1 expression in QBC939 cells. RESULTS: Here we reported that FOXO1, acetylation of FOXO1 (Ac-FOXO1) and the following interaction between Ac-FOXO1 and Atg7 regulated the basal and serum starvation (SS)-induced autophagy as evidenced by light chain 3 (LC3) accumulation and p62 degration. Either treatment with FOXO1 siRNA or resveratrol, a sirt1 agonist, inhibited autophagic flux, resulting in oxidative stress, mitochondrial dysfunction (MtD) and apoptosis in QBC939 cells, which were attenuated by enhancing autophagy with rapamycin. On the contrary, inhibiting autophagic flux with 3-MA worsened all these effects in QBC939 cells. CONCLUSIONS: Taken together, our study for the first time identified FOXO1 as a potential therapeutic target to cure against human cholangiocarcinoma via regulation of autophagy, oxidative stress and MtD.

Protein coding sequences account for around 3% of the human genome, the rest are noncoding RNA (ncRNA) including long ncRNA (lncRNA) and miRNA. Accumulating evidence indicates that lncRNAs and miRNAs are candidate biomarkers for diagnosis, prognosis and therapy of cardiovascular diseases. The lncRNAs act as sponge-like effects on numerous miRNAs, subsequently regulating miRNAs and their targets, mRNA functions. The role of lncRNA-miRNA-mRNA axis in pathogenesis of cardiovascular diseases has been recently reported and highlighted. Herein, this review discusses emerging roles of lncRNA-miRNA-mRNA axis in cardiovascular pathophysiology and regulation, with a novel focus on cardioprotective network activities of the two subgroup ncRNAs.

OBJECTIVE: Growing evidence has shown that vitamin D deficiency can cause lower bone mineral density (BMD) and an increased risk of osteoporosis. Vitamin D receptor (VDR) BsmI polymorphism (rs1544410) can affect BMD variation and circulating osteocalcin levels. To date, a wide range of epidemiological studies have been carried out to evaluate the association between VDR BsmI polymorphism and susceptibility to osteoporosis. Conflicting results, however, were obtained. The aim of this study was to evaluate the effect of VDR BsmI polymorphism on osteoporosis risk using a meta-analysis. METHODS: Twenty-six publications were identified by searching PubMed and Embase databases. The association between VDR BsmI polymorphism and osteoporosis was estimated by calculating pooled odds ratios (ORs) with corresponding 95% confidence intervals (CIs). RESULTS: The bb genotype was associated with a significantly decreased risk of osteoporosis in overall comparison (bb vs. BB: OR=0.61, 95% CI, 0.40-0.92; bb vs. BB/Bb: OR=0.70, 95% CI, 0.52-0.95, respectively). Subgroup analyses showed that the bb genotype had a decreased risk of developing osteoporosis in postmenopausal women (bb vs. BB/Bb: OR=0.68, 95% CI, 0.46-0.98) and Africans (Bb/bb vs. BB: OR=0.18, 95% CI, 0.09-0.37). CONCLUSION: The VDR BsmI polymorphism may have a protective role against the development of osteoporosis.

OBJECTIVES: To describe the clinical characteristics and management of patients hospitalised with community-acquired pneumonia (CAP) in China. DESIGN: This was a multicentre, retrospective, observational study. SETTING: 13 teaching hospitals in northern, central and southern China from 1 January 2014 to 31 December 2014 PARTICIPANTS: Information on hospitalised patients aged ≥14 years with radiographically confirmed pneumonia with illness onset in the community was collected using standard case report forms. PRIMARY AND SECONDARY OUTCOME MEASURES: Resource use for CAP management. RESULTS: Of 14 793 patients screened, 5828 with radiographically confirmed CAP were included in the final analysis. Low mortality risk patients with a CURB-65 score 0-1 and Pneumonia Severity Index risk class I-II accounted for 81.2% (4434/5594) and 56.4% (2034/3609) patients, respectively. 21.7% (1111/5130) patients had already achieved clinical stability on admission. A definite or probable pathogen was identified only in 12.7% (738/5828) patients. 40.9% (1575/3852) patients without pseudomonal infection risk factors received antimicrobial overtreatment regimens. The median duration between clinical stability to discharge was 5.0 days with 30-day mortality of 4.2%. CONCLUSIONS: These data demonstrated the overuse of health resources in CAP management, indicating that there is potential for improvement and substantial savings to healthcare systems in China. TRIAL REGISTRATION NUMBER: NCT02489578; Results.

BACKGROUND: Pain and cartilage destruction caused by osteoarthritis (OA) is a major challenge in clinical treatment. Traditional intra-articular injection of hyaluronic acid (HA) can relieve the disease, but limited by the difficulty of long-term maintenance of efficacy. METHODS: In this study, an injectable and self-healing hydrogel was synthesized by in situ crosslinking of N-carboxyethyl chitosan (N-chitosan), adipic acid dihydrazide (ADH), and hyaluronic acid-aldehyde (HA-ALD). RESULTS: This supramolecular hydrogel sustains good biocompatibility for chondrocytes. Intra-articular injection of this novel hydrogel can significantly alleviate the local inflammation microenvironment in knee joints, through inhibiting the inflammatory cytokines (such as TNF-α, IL-1β, IL-6 and IL-17) in the synovial fluid and cartilage at 2- and even 12-weeks post-injection. Histological and behavioral test indicated that hydrogel injection protected cartilage destruction and relieved pain in OA rats, in comparison to HA injection. CONCLUSION: This kind of novel hydrogel, which is superior to the traditional HA injection, reveals a great potential for the treatment of OA.

Limited information exists on the clinical characteristics predictive of mortality in patients aged ≥65 years in many countries. The impact of adherence to current antimicrobial guidelines on the mortality of hospitalized elderly patients with community-acquired pneumonia (CAP) has never been assessed. A total of 3131 patients aged ≥65 years were enrolled from a multi-center, retrospective, observational study initiated by the CAP-China network. Risk factors for death were screened with multivariable logistic regression analysis, with emphasis on the evaluation of age, comorbidities and antimicrobial treatment regimen with regard to the current Chinese CAP guidelines. The mean age of the study population was 77.4 ± 7.4 years. Overall in-hospital and 60-day mortality were 5.7% and 7.6%, respectively; these rates were three-fold higher in those aged ≥85 years than in the 65–74 group (11.9% versus 3.2% for in-hospital mortality and 14.1% versus 4.7% for 60-day mortality, respectively). The mortality was significantly higher among patients with comorbidities compared with those who were otherwise healthy. According to the 2016 Chinese CAP guidelines, 62.1% of patients (1907/3073) received non-adherent treatment. For general-ward patients without risk factors for Pseudomonas aeruginosa (PA) infection (n = 2258), 52.3% (1094/2090) were over-treated, characterized by monotherapy with an anti-pseudomonal β-lactam or combination with fluoroquinolone + β-lactam; while 71.4% of intensive care unit (ICU) patients (120/168) were undertreated, without coverage of atypical bacteria. Among patients with risk factors for PA infection (n = 815), 22.9% (165/722) of those in the general ward and 74.2% of those in the ICU (69/93) were undertreated, using regimens without anti-pseudomonal activity. The independent predictors of 60-day mortality were age, long-term bedridden status, congestive heart failure, CURB-65, glucose, heart rate, arterial oxygen saturation (SaO2) and albumin levels. Overtreatment in general-ward patients and undertreatment in ICU patients were critical problems. Compliance with Chinese guidelines will require fundamental changes in standard-of-care treatment patterns. The data included herein may facilitate early identification of patients at increased risk of mortality. The study was registered at ClinicalTrials.gov ( NCT02489578 ).